HIV1 strains exhibit a wide range of sequence heterogeneity which modulates cell tropism. Tropism for monocytes is likely to affect manifestations of HIV1 infection, whereas tropism for T lymphoid cell lines correlates with disease progression. The current study focuses on the relationship of sequence heterogeneity to alterations in tropism. It is aimed at elucidating the molecular basis for cell tropism by identifying the critical viral determinants involved and their function with respect to HIV1 infection and replication. Viral determinants in or near the V3 loop of envelope, vpr, and vpu will be examined for their effects on monocyte infection. Determinants responsible for infection of T lymphoid cell lines will be identified. The function of these determinants will be analyzed with respect to the step in the virus replicative cycle that is modulated. In addition, the structure, expression, and function of the envelope proteins from clones exhibiting, or not exhibiting specific tropism will be analyzed in recombinant vaccinia viruses and in highly purified form as expressed in Drosophila tissue culture. These studies will provide new insights into the molecular basis of HIV1 tropism which will increase our understanding of disease pathogenesis.